Design, synthesis and biological evaluation of photoaffinity probes of antiangiogenic homoisoflavonoids

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• 作者：Bit Lee^a ; Wei Sun^a ; Hyungjun Lee^a ; Halesha Basavarajappa^b ; ^c ; Rania S. Sulaiman^b ; ^d ; ^e ; Kamakshi Sishtla^b ; Xiang Fei^a ; Timothy W. Corson^b ; ^c ; ^d ; Seung-Yong Seo^a ; ^{syseo@gachon.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ZTJOCDUDIVQZDR-DVNQVLBESA-N ; WFUYFBBPPFFWLK-WVZVNDETSA-N ; RWTLHADKCUBLTO-DKGAOUFQSA-N ; RGPIPIBZRORUEM-ZWXIRZRQSA-N ; VEPJZBUPJUWVJA-UHFFFAOYSA-N ; ZWFOOMQCYIGZBE-ZOBUZTSGSA-N ; RBXKAWIISCLQSK-LYDQXETESA-N ; NGDOHYUFIMQHRU-SZKYPABLSA-N ; QPXDJAQCABFFAR-UHFFFAOYSA-N ; RWCKRMUJXXKJEB-UHFFFAOYSA-N ; TUQKLBWLGCQDIJ-UHFFFAOYSA-N ; ISJHHJHYFYWFDW-TXDWVUBVSA-N ; HGDNGCZFUISJOH-YANBTOMASA-N ; PWDLOLIMTJICSA-GITCGBDTSA-N ; ZGCVIOKBSBFQDN-UHFFFAOYSA-N ; BCWMYSCFOVBMIW-JFINJBMXSA-N ; KIHYEXJCXWTUIW-FHZUCYEKSA-N ; FZEGFZN
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 September 2016
• 年：2016
• 卷：26
• 期：17
• 页码：4277-4281
• 全文大小：720 K

文摘

A naturally occurring homoisoflavonoid, cremastranone (1) inhibited angiogenesis in vitro and in vivo. We developed an analogue SH-11037 (2) which is more potent than cremastranone in human retinal microvascular endothelial cells (HRECs) and blocks neovascularization in animal models. Despite their efficacy, the mechanism of these compounds is not yet fully known. In the course of building on a strong foundation of SAR and creating a novel chemical tool for target identification of homoisoflavonoid-binding proteins, various types of photoaffinity probes were designed and synthesized in which benzophenone and biotin were attached to homoisoflavanonoids using PEG linkers on either the C-3′ or C-7 position. Notably, the photoaffinity probes linking on the phenol group of the C-3′ position retain excellent activity of inhibiting retinal endothelial cell proliferation with up to 72 nM of GI₅₀.